Vitiligo is a common acquired depigmentary skin disorder occurring in about
1% of the world's population, regardless of age, sex and skin color. It results
from melanocyte destruction with loss of melanin which causes sharply demarcated
depigmented skin macules. The basic pathogenesis remains unknown (Mosher
et al., 1993).
A number of therapeutic options for repigmentation of vitiligo are available.
Treatments, such as topical steroids, Psoralen Plus Ultraviolet A (PUVA) and
narrowband (311 nm) UVB (NB-UVB) are currently the most widely used but yield
unsatisfactory results in all or most of cases (Taneja,
Surgical therapies can be used alone or in conjunction with medical therapy
to achieve repigmentation in cases refractory to medical treatment, provided
that the disease is stable. Surgical treatment options for vitiligo offer the
potential for rapid and more desirable amounts of repigmentation. The different
modalities of surgical techniques include organ-cultured fetal skin allografting,
epidermal culture grafting, melanocyte culture grafting, autologous noncultured
melanocyte-keratinocyte cell transplantation, epidermal grafting by the suction
blister technique, thin Thiersch split skin grafting or miniature punch grafting.
These methods depend on transplant of melanocytes from areas of normal skin
to the vitiliginous patches (Falabella, 1989; Van
Geel et al., 2001; Ozdemir et al., 2002;
Yaar and Gilchrest, 2001; Rusfianti
and Wirohadidjodjo, 2006).
The 308 nm excimer laser emits a monochromatic light of 308 nm and induces
photobiological effects similar to NB-UVB, thus stimulating adjacent melanocytes
in the outer root sheath of hair follicles and on the margins of lesions to
migrate and repopulate the vitiliginous areas. Several studies have shown the
response of vitiligo patches to excimer laser and United States (US) Food and
Drug Administration (FDA) has approved it for the treatment of vitiligo and
psoriasis (Homan et al., 2011; Nicolaidou
et al., 2009; Hofer et al., 2006;
Casacci et al., 2007; Al-Mutairi
et al., 2010). Excimer laser permits the selective treatment of only
lesional skin in a small number of treatment sessions over a short period of
time and ensures no unnecessary radiation of healthy skin. Thus the patient
receives less radiation, reducing the risk of skin aging and carcinogenesis.
Furthermore, the unsightly tanning of all perilesional skin is avoided (Casacci
et al., 2007).
Combination of grafting and other nonsurgical modalities such as PUVA (Skouge
et al., 1992; Barman et al., 2004)
and narrow-band UVB (NB-UVB) (Lahiri et al., 2006)
have been used to achieve further repigmentation with better and faster results
than monotherapy. Similarly, fewer studies reported that punch grafting or split-skin-thickness
grafting followed by excimer laser was found to be effective in inducing repigmentation
in vitiligo patients (Homan et al., 2011; Al-Mutairi
et al., 2010). In most of these studies, the results were evaluated
only in terms of extent of pigmentation. Complications and color match were
evaluated separately. This approach, however, may not give a fair idea about
This study was done to evaluate the results of combined treatment of stable
focal and segmental vitiligo with punch minigrafting followed by postoperative
MATERIALS AND METHODS
Patients: Thirty patients with focal stable or segmental vitiligo were
enrolled in this study. The patients were seen during the period from January
2007 to October 2009. In patients with stable focal vitiligo, only one site
was selected for the study. Stable vitiligo was defined as no progression of
existing lesions or no appearance of new lesions during the previous 12 months,
absence of the Koebner phenomenon and a positive minigrafting test which was
done according to Falabella et al. (1995). A
minigraft test was performed by implanting two minigrafts (2 mm) in the lesions
to be grafted. Patients with 1 to 2 mm spread of pigment beyond the graft margins
after 3 months were selected for final transplantation.
Exclusion criteria included a large vitiliginous patch, history of hypertrophic
scarring and/or keloid, koebnerization and bleeding diathesis. Certain areas
such as body folds, fingers, toes, palms, soles, lips, eyelids, nipples and
areola, elbows, knees and genitals were considered difficult to treat sites
and were excluded, due to the difficulty in immobilizing the treated area. Also,
pregnant women, patients receiving immunosuppressive therapy and patients with
obsessive or compulsive attitudes toward their pigmentary defect, especially
when they are excessively concerned about their aesthetic alterations, were
excluded from the study.
All participants provided signed informed consent. Information about each patients
name, age, sex, occupation and contact details were noted on a form. A detailed
medical history, general examination and systemic evaluation were performed
in all the patients to exclude any other concomitant dermatological or medical
disorders. All patients had a baseline photograph taken. A baseline investigation,
including complete blood count, differential count and coagulation profile,
was performed on all patients.
Preparation of donor site: The site used was the lateral aspect of thigh
or the lateral-upper area of the arm. After shaving off the hairs and proper
cleansing with povidone iodine and 70% ethanol, the area was anaesthetized with
1% xylocaine with epinephrine. Two millimeter punches were used to prepare the
donor chambers. The chambers were made at a distance of 3-4 mm from each other
(Fig. 1). The depth of the donor grafts should not include
the subcutaneous fat. If it is present, it was trimmed off. The number of the
minigrafts was decided according to the size of the recipient vitiliginous area.
Figure 1 shows donor site on the lateral upper arm immediately
after taking nine 2 mm punch grafts in one of our patients with stable focal
vitiligo on the right leg. The donor grafts were immersed in a petri dish containing
normal saline, till preparation of the recipient site. The defects created at
the donor sites were then covered with normal dressing for 10 days.
Preparation of recipient site and postoperative care: The recipient
site was prepared and anaesthetized as done at the donor site. Similar number
of punch grafts was removed from the recipient site using the same size of punches.
The tissues removed from the recipient site were taken 1 mm deeper than that
taken from the donor site to reduce the possibility of cobble-stone appearance.
Hemostasis was achieved by pressing a saline-soaked gauze piece over the area.
Donor grafts were then placed at the holes created at the recipient site which
was done at a distance of 8-10 mm (Fig. 2). Care was taken
to ensure that the graft is not folded and the tissue is not crushed or placed
upside down. The needle of the syringe or the tip of the scissors was used for
the proper placement of grafts in the recipient chambers. The grafts were then
fixed at the recipient site using a fixing spray (Opsite®,UK)
by applying the spray to the surface of the grafts at a distance of 15 cm and
then left for 5 min before dressing.
|| Patient at donor site immediately after taking the minigrafts
|| Patient with focal vitiligo immediately after PMG procedure
Figure 2 shows seven donor minigrafts immediately after it
was placed at the holes created at the recipient site on the right hand of one
of our patients. The holes were done at a distance of 8-10 mm on the vitiliginous
After placing the punch grafts in the acceptor site, both the acceptor and
donor sites were covered with steri-strip and bio-occlusive micropore. Immobilization
of the recipient area was then done using a pressure bandage. Dressings were
opened after 24 h to look for any dislodgement of grafts. Patients were advised
to avoid excessive movement of the grafted area. Systemic antibiotics were not
given routinely except in diabetic patients with large number of grafts. Two
weeks after surgery, the dressing was removed and patients were asked to apply
topical antibiotic cream twice daily for another one week.
Excimer laser: A monochromatic 308 nm xenon chloride (XeCl) excimer
laser (Talos, WaveLight®,
Germany) was used. The laser was operated with pulse repetition frequency of
200 hertz (Hz) and impulse energy of 6.5 mJ. The pulse width was 60 nsec. Laser
light was delivered through an articulated mirror arm to a handpiece with spot
diameters of 15, 20 and 25 mm that was changed according to the size of the
treated lesions. Excimer laser was administered three times weekly but never
on 2 consecutive days, for an average of 8 weeks. Treatment was started with
100 mJ-2 centimeter (mJ cm-2) for body lesions and 50
mJ cm-2 for the face and neck. This was increased by 50 mJ cm-2
per sitting until erythema appeared. If erythema remained less than 48 h, the
dose was kept the same. If erythema persisted more than 48 h, the dose was reduced
to the last well-tolerated one. Whenever burning or blistering developed, a
treatment was skipped. The eyes were protected with UV-protective goggles. Only
the application of emollients was allowed during the study.
Response assessment: Final assessment of the response was done one year
after the transplantation procedure which is a sufficient time for the emergence
of the final picture of the surgical procedures. The scoring system in this
study was similar to that suggested by Gupta et al.
(2002). They have developed a scoring system with holistic approach considering
the extent of pigmentation, color match and the complications of the donor and
the recipient areas, all taken together. In this scoring system, the score for
individual criteria was multiplied with a factor, the value of which was decided
on the basis of relative importance of each criterion. The extent of pigmentation
and color match was multiplied with a positive factor (x5 and x3, respectively),
while the complications of both the donor and the recipient areas were multiplied
with a minus factor (x-2 and x-3, respectively). The scoring was done by two
independent observers who are regularly involved in the surgical correction
of vitiligo. The final results of the evaluation by both investigators were
identical in all the patients. Patients were also asked to judge the results
of punch grafting as excellent, good, fair or poor. Furthermore, they were asked
if they would recommend punch grafting to other patients with vitiligo.
Statistical analysis: The data were analysed using the statistical package
SPSS version 15.0. The data were described using the mean for quantitative data
and percent for qualitative data. Statistical analysis was performed using chi-square
(χ2) test. The significant level was set at p<0.05.
This study included 30 patients (16 female and 14 male) with focal stable or
segmental vitiligo. All the patients were treated with 2 mm punch grafting in
combination with excimer laser. Eleven patients had segmental vitiligo and 19
with focal vitiligo. Eight of the treated lesions were on the head and neck,
three on the hands, three on the foot, three on the trunk, six on the legs,
six on the arms and one on the thigh. Three individuals with focal vitiligo
vulgaris had hyperthyroidism and one had hypothyroidism. In the segmental group,
none of the individuals had any endocrinal abnormalities.
The patients characteristics
are shown in Table 1. All the patients had received various
therapies in the past, including topical steroids, PUVA, NB-UVB, topical calcineurin
inhibitors and excimer laser with minimal or partial response. Some patients
received combination of therapies. None of the patients had received surgical
treatment. The period for which the disease was clinically inactive ranged from
one up to 10 years (mean of 2.54 years).
Investigators global assessment for evaluation of the final response
was done one year after surgery using the scoring proposed by Gupta
et al. (2002). Sixteen patients (53.33%) were given a score of 17
to 21(excellent response) (Fig. 3), 12 patients (40%) given
a score of 12 to 16(good response) and 2 patients (6.66%) given a score of 7
to 11 (fair response). So, 93.33% of patients were assessed to have an outcome
ranging from good to excellent (Table 1). Figure
3a shows a 20-year-old male with segmental vitiligo on the left upper leg
before treatment (recipient site). Figure 3b shows the same
patient 12 months after punch minigrafting (PMG) and excimer laser with excellent
results regarding both pigmentation and color matching, with no evidence of
any complications either at donor or recipient sites.
Seven of 11 patients with segmental vitiligo (63.36%) showed excellent response
according to investigators global
assessment (Table 2). Of the 19 patients with focal vitiligo,
9 patients (47.36%) showed excellent response. The comparison between both groups
was not statistically significant (Table 2). Of 14 patients
having age of 30 years or below, 11 of them (78.57%) showed excellent response,
while of 16 patients aged more than 30 years, only 5 of them (31.25%) showed
excellent response (Table 2). This difference was statistically
significant with p<0.05 (χ2 test) (Table 2).
|| (a) A 20-year-old male with segmental vitiligo before treatment
(recipient site) and (b) Same patient 12 months after PMG and excimer laser
showing excellent results
|| Patient characteristics and response to treatment according
to investigators global assessment
Patients global assessment
were as follow: 15 as excellent (50%), 12 as good (40%) and 3 as fair results
(10%). So, 90% of patients assessed their outcome ranging from good to excellent
(these results were not shown in a table).
The complications observed during the study were minimal. It occurred in 5
patients (16.66%).Two patients developed depigmentation at the donor site, whereas
the transplanted areas retained the pigment.
|| Effect of age group and type of vitiligo on the percentage
of excellent response analyzed by chi-square (χ2) test
|*Values are significant at p≤0.05
Two patients developed cobble-stoning. One patient developed infection followed
by keloid formation at the donor site. None of the patients developed depigmentation
of the transplanted skin during the follow-up period till one year post-operative.
Currently, the modalities of vitiligo treatment, especially dermatosurgery,
have increased slowly but steadily. There are several techniques, ranging from
simple to complicated and sophisticated approaches (Rusfianti
and Wirohadidjodjo, 2006). Punch grafting is a widely used method in treating
vitiligo, as it is relatively inexpensive and easy to perform (Falabella
and Barona, 2009). However, after punch grafting, the pigment spread takes
its own time that may be several months. Ultraviolet radiation following punch
grafting may stimulate the migration of melanocytes from the grafts into the
vitiliginous skin, thereby increasing the rate of repigmentation. So, combination
treatment with grafting and postsurgical PUVA or NB-UVB therapy has been used
to augment and speed the rate of pigmentation (Barman et
al., 2004; Homan et al., 2011; Lahiri
et al., 2006).
The 308 nm excimer laser emits a monochromatic light of 308 nm and induces
photobiological effects similar to NB-UVB but with fewer side effects. So, this
study was done to study the results of combined treatment of stable focal and
segmental vitiligo with punch minigrafting followed by postoperative excimer
three times weekly for 24 settings.
In the present study, the results were assessed using a novel scoring system
suggested by Gupta et al. (2002), for evaluation
of results of autologous transplantation methods in vitiligo. They considered
that comparison of different studies of vitiligo surgery carried out at different
centers may be difficult in the absence of uniform evaluation criteria. In most
of the published studies, the results were evaluated in terms of extent of pigmentation.
Complications and color match were evaluated separately. This approach, however,
may not give a fair idea about the results. Gupta et
al. (2002) have developed a scoring system considering the extent of
pigmentation, color match and the complications of both the donor and the recipient
areas, all taken together. They applied this scoring system on twelve patients
who underwent thin Thiersch split skin grafting (TSTG) (2 patients), Suction
Blister Grafting (SBG) (3 patients) and Punch Minigrafting (PMG) (7 patients).
The results among 7 patients who underwent PMG showed that 5 of 7 patients (71.42%)
had good to excellent outcome. In contrast, the results of this study showed
that 93.33% of patients were assessed to have an outcome ranging from good to
excellent, after the same period of follow-up (1 year). This difference may
be explained by the additional effect of postoperative excimer laser which was
used by us to augment pigment spread after minigrafting.
In a prospective study by Lahiri et al. (2006)
which included 66 individuals with stable, refractory vitiligo, repigmentation
with punch grafting followed by NB-UVB was evaluated. The patients were followed
up for a maximum period of 18 months after grafting. They found that repigmentation
was achieved in only 57 (86.36%) cases, in spite of longer period of follow
up after surgery. This was in contrast to the present study which showed that
repigmentation was achieved in all patients (100%). So, postoperative enhancement
of pigment spread using excimer laser appears to be superior to that of NB-UVB.
Homan et al. (2011), found that punch grafting
followed by excimer laser or NB-UVB induced a comparable grade of repigmentation
with no statistically significant difference between both modalities after 3
months follow up. They concluded that choice between excimer laser and NB-UVB
cannot solely be based on repigmentation but rather on other factors, such as
patients preferences, cumulative dose, availability, ease of administration
and costs. However, given the lower UV dose of excimer laser, they recommend
its use in vulnerable populations, such as in small children and patients with
sun-damaged skin with a history of long-term UVB treatment.
Al-Mutairi et al. (2010), treated 17 patients
with stable focal or segmental vitiligo with split-skin-thickness grafting followed
by 32 sessions of 308 nm excimer laser. All seventeen patients showed repigmentation
and overall results were graded as excellent in 12 patients (70.58%) and good
in the other five (29.4%) when evaluated one year after surgery patients. The
percentage of excellent pigmentation in the present study (53.33%) was lower
than the results of Al-Mutairi et al. (2010)
and this may be attributed to different technique of grafting and due to different
method of evaluation.
In this study, 63.36% of patients with segmental vitiligo (7/11) showed excellent
response in contrast to 47.36% of patients with focal vitiligo (9/19) who showed
the same response. However, this difference was not statistically significant
due to small number of patients. To our knowledge, there are no controlled trials
yet done to compare the difference in treatment response among patients with
segmental and focal vitiligo, using combined surgical therapy and excimer laser.
Generally, patients with segmental vitiligo are considered good candidates for
surgical treatment. In a recent study by Kato et al.
(2011), the results suggested that 1-mm minigrafts were effective for treating
patients with vitiligo with better results occurred in patients with segmental
and limited subtypes. Although medical treatment is often helpful in segmental
vitiligo, complete repigmentation is almost always difficult to obtain. Thus,
surgical treatment is necessary for complete repigmentation in many cases of
segmental vitiligo (Falabella and Barona, 2009).
In the present study, excellent response was achieved in 78.57% (11/14) of
patients aged 30 year or below, while of 16 patients aged more than 30 years,
only 5 of them (5/16, 31.25%) showed excellent response. This difference was
statistically significant. These results were in agreement with other studies.
Kato et al. (2011), found that repigmentation
covered a broader area and occurred more quickly in patients under 15 years
of age than in those over 20 years of age. In a recent study by Feetham
et al. (2012) who used different post-operative treatments following
punch minigrafting, they concluded that Patients younger than 20 years achieved
the greatest average improvement in repigmentation whereas those aged 60 and
older showed the least improvement.
Punch grafting is a useful treatment modality for many patients with stable
vitiligo who are not responding to other treatment options, with most patients
showing some degree of improvement. It is simple, easy to perform with minimal
complications. Combination treatment with autologous punch minigrafting and
postsurgical exposure to 308 nm excimer laser in patients with stable focal
or segmental vitiligo can lead to fast, cosmetically satisfying results for
both physicians and patients. As a treatment variable, segmental vitiligo and
vitiligo in patients younger than 30 years achieved the greatest average improvement
This study may provide an evidence that monotherapy of stable recalcitrant
vitiligo with punch grafting should be changed to a combination regimen with
excimer laser to get the benefit of faster and more excellent repigmentation
which can dramatically improve the quality of life of the patients. Further
prospective studies on larger number of patients should be done to determine
the effect of other variables, as skin color of patient, site to be treated
and punch size used, with longer period of follow-up to determine the stability
of pigmentation achieved by this combination regimen.